Professor Michael Eccles, head of the Developmental Genetics Laboratory in the Department of Pathology, says Pax2 had already been implicated in certain forms of kidney cancer, as well as a syndrome in which low levels of the gene leave kidneys underdeveloped.
"But we also wondered if it played a part in other diseases," he says.
"That's part of the reason why we decided to look at PKD - there was some suggestion Pax2 might be involved in cyst formation.
"The hands-on research, led by research fellow Dr Cherie Stayner, was published late last year in the Oxford-based journal, Human Molecular Genetics.
She began by crossing two types of mice: one had a mutation in the Pax2 gene that reduced its expression during development, while the other had a PKD mutation that meant Pax2 was not switched off.
Eccles says that by crossing the two they could then see if there was an interaction between those two genes.
"We found that the cysts in mice carrying both the Pax2 and PKD mutations became much smaller, and that these small cysts no longer had Pax2 being expressed.
"So, whatever we were doing was not only fixing the size of the cysts in the kidneys, it was actually fixing the problem with the Pax2 as well."Stayner says these findings also appear to be relevant to human disease.
"We looked at human tissue as well. We saw very strong expression of Pax2 in the cystic kidney - and normally you don't see much Pax2 expression in the adult kidney of humans or mice," she says.
"So if we lower Pax2, is this going have an effect on cystic disease?"
Autosomal dominant polycystic kidney disease (ADPKD) affects between 1 in 400 and 1 in 1000 people and there is no effective direct treatment.
A key feature of the disease is the end-stage renal failure, which means by the time they are in their mid-50s half the people with ADPKD have end-stage renal disease, the eventual cause of death.
"You can take steps to maintain kidney function, but there is no way of stopping the cysts from growing at present," says Stayner.
"The main options are usually dialysis or renal transplantation."Eccles and Stayner say they hope that they can get some ideas on possible new treatments by studying the Pax2 gene or the pathways it acts on.
They have key collaborations with Professor Jing Zhou (Brigham and Women's Hospital, Harvard Medical School, Boston, USA) and Professor Paul Goodyer (Montreal Children's Hospital Research Institute, Quebec, Canada), and are now seeking funding to further investigate ways of inhibiting the gene.
FUNDING
Foundation for Research, Science and Technology Postdoctoral FellowshipHealth Research Council